Loneliness increases the risk of poor sleep, higher blood pressure, cognitive and immune decline, depression, and ultimately an earlier death. Why? The traditional explanation is that lonely people lack life’s advisors: people who encourage healthy behaviours and curb unhealthy ones. If so, we should invest in pamphlets, adverts and GP advice: ignorance is the true disease, loneliness just a symptom.

But this can’t be the full story. Introverts with small networks aren’t at especial health risk, and people with an objectively full social life can feel lonely and suffer the consequences. A new review argues that for the 800,000 UK citizens who experience it all or most of the time, loneliness itself is the disease: it directly alters our perception, our thoughts, and the very structure and chemistry of our brains. The authors – loneliness expert John Cacioppo, his wife Stephanie Cacioppo, and their colleague John Capitanio – build their case on psychological and neuroscientific research, together with animal studies that help show loneliness really is the cause, not just the consequence, of various mental and physical effects.

The review suggests lonely people are sensitive to negative social outcomes and accordingly their responses in social settings are dampened. We know the former from reaction time tasks involving negative social words (lonely people respond faster), and tasks involving the detection of concealed pain in faces (lonely people are extra sensitive when the faces are dislikeable). Functional imaging evidence also shows lonely people have a suppressed neural response to rewarding social stimuli, which reduces their excitement about possible social contact; they also have dampened activity in brain areas involved in predicting what others are thinking – possibly a defence mechanism based on the idea that it’s better not to know. All this adds up to what the authors characterise as a social “self-preservation mode.”

Meanwhile, animal models are helping us to understand the deeper, biological correlates associated with loneliness. For mice, being raised in isolation depletes key neurosteroids including one involved in aggression; it reduces brain myelination, which is vital to brain plasticity and may account for the social withdrawal and inflexibility seen in isolated animals; and it can influence gene expression linked to anxious behaviours.

What about changes to our neural tissue? Human research is suggestive: in one study, people who self-identified as lonelier were more likely to develop dementia. Here, initial cognitive decline could be causing loneliness, but animal work gives us some plausible mechanisms for loneliness’ impact: animals kept in isolation have suppressed growth of new neurons in areas relating to communication and memory, just as very social periods such as breeding season see a pronounced spike in growth.

Other basic brain processes are also upset by isolation. Isolated mice show reduced delta-wave activity during deep sleep; and their inflammatory responses also change, meaning that in one study, three in five isolated mice died following an induced stroke, whereas every one of their cage-sharing peers survived the same process.

The research is clear that loneliness directly impacts health, so we need to do what we can to help people free themselves from social marginalisation. I’ve seen one approach during my time serving with time banking charities, in which people give their own time in return for someone else’s in a different situation – a process that can build social networks. Also the issue is acquiring momentum through the Campaign to End Loneliness and technology solutions such as the RSA’s Social Mirror project – an app that tells people about local social groups and activities. Mainstream health is also picking this up under the term “social prescription” (physicians advise patients of social groups and activities and “facilitators” help the patients take up the opportunities). But amongst all the institutional activity, we mustn’t forget our individual duties: sometimes all that’s needed is to reach out.